This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aberrant Wnt/[unreadable]-catenin signal transduction is involved in many diseases. In colorectal cancer and melanoma, mutational disruption of proteins involved in the degradation of [unreadable]-catenin, the key effector of the Wnt signaling pathway, results in stabilization of [unreadable]-catenin and, in turn, activation of transcription. We are employing tandem-affinity protein purification and mass spectrometry to define the protein interaction network of the [unreadable]-catenin destruction complex.